The long-term goal of the proposed research is to contribute to the understanding of relationships between metabolism and toxicity of pesticides, particularly as they are related to toxic interactions. Research will be conducted on the reactivities of organophosphorus insecticides and anilide herbicides with tissue hydrolases from a variety of species including human tissues. This type of information should help in extrapolation of toxicity and interaction data from standard laboratory animals to other non-target species. Other experiments will be directed at revealing the relative importance of oxidative, hydrolytic, and transferase enzymes in the metabolism of organophosphorus insecticides in mammalian and fish species. The interaction of other chemicals, as piperonyl butoxide, and dietary esterases, as copper deficiency, with these enzyme systems will be examined with respect to mechanisms of potentiation or antagonism of phosphorothionate toxicity. Possible subtle functional effects of phosphorothionate insecticides and potential residue metabolites will also be sought. This research should be of value both in identifying potential interactions among pesticides and providing basic biochemical guidelines useful for consideration of the practical significance of these interactions to non-target species.